Therapy of metastatic pancreatic neuroendocrine tumors (pNETs): recent insights and advances

Abstract

Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years.

Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: a nationwide survey analysis

“…Regarding NET, functionality, invasion depth, and the presence or absence of metastases must be correctly evaluated and treatment administered on the basis of the degrees of differentiation and malignancy of the tumor [4,[34][35][36]. Although surgical total excision is the standard treatment [37], some studies report that when radical treatment is difficult, debulking surgery of primary lesions and liver metastatic lesions effectively alleviate symptoms and improve prognosis [4,34,37]. On the other hand, in cases of unresectable advanced tumors, treatment aiming to improve prognosis by inhibiting tumor growth and improving clinical symptoms is necessary [8,13,27].…”

“…Although the reasons for this increase are unclear, the recognition of the disease and improved diagnostic technology may be partially responsible. Thus, continued accumulation and examination of data regarding the trend of the actual number of patients is necessary [3,4].…”

Pancreatic Neuroendocrine Neoplasms: Basic Biology, Current Treatment Strategies and Prospects for the Future

“…Surgical resection with regional lymph node dissection is the only curative treatment option, and is recommended to all patients with early-stage well-differentiated pNENs [41][42][43]. Although cancer patients with metastatic diseases are generally unsuitable for surgical resection in the field of oncology, partial hepatectomy is often performed in pNENs patients with liver metastases, depending upon the number, size and location of the lesions, the extent of the primary tumor and the patient's performance status [43].…”

Pancreatic Neuroendocrine Tumors: an Update

“…Nevertheless, according to recent studies, less than 15 % of patients presenting with metastatic disease are eligible for a debulking procedure [59,62] as no survival advantage has been shown in patients receiving suboptimal debulking (<90 % of disease burden) [62][63][64]. Unfortunately, even after removal of all metastatic disease with microscopic negative margin (R0), the recurrence (or persistence) rate remains high with 1-year and 5-year disease free survival (DFS) of 53.7 and 10.7 %, respectively [23].…”

“…Portal vein thrombosis, ascites, and liver failure are absolute contraindications for TAE/TACE. It is worth noting that diffuse metastatic disease, involving more than 50 % of the liver parenchyma, represents a relative contraindication to TAE/TACE as episodes of acute liver failure are known to occur [5,62,76]. In the setting of extensive liver disease, radioembolization (RE) is a valuable alternative to TAE/TACE.…”